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Antimicrobial Peptides Targeting Oral Pathogens: Applicability as an Oral Disease Treatment and Dental Material
J Dent Hyg Sci 2024;24:231-48
Published online December 31, 2024;  https://doi.org/10.17135/jdhs.2024.24.4.231
© 2024 Korean Society of Dental Hygiene Science.

Sehyeok Im1 ,2, Jun Hyuck Lee1 ,2,†,*, and Youn-Soo Shim3,†,*

1Division of Life Sciences, Korea Polar Research Institute, Incheon 21990, 2Department of Polar Sciences, University of Science and Technology, Incheon 21990, 3Department of Dental Hygiene, Sunmoon University, Asan 31460, Korea
Correspondence to: Jun Hyuck Lee, https://orcid.org/0000-0002-4831-2228
Division of Life Sciences, Korea Polar Research Institute, 26 Songdomirae-ro, Yeonsu-gu, Incheon 21990, Korea
Tel: +82-32-760-5555, Fax: +82-32-760-5509, E-mail: junhyucklee@kopri.re.kr
Youn-Soo Shim, https://orcid.org/0000-0002-2894-2441
Department of Dental Hygiene, Sunmoon University, 70 Sunmoon-ro 221 beon-gil, Tangjeong-myeon, Asan 31460, Korea
Tel: +82-41-530-2740, Fax: +82-41-530-2726, E-mail: ysshim@sunmoon.ac.kr
*These authors contributed equally to this work.
Received November 4, 2024; Revised November 23, 2024; Accepted November 28, 2024.
This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract
Background: Antimicrobial peptides (AMPs) are small, naturally occurring molecules that are integral components of the innate immune system across many organisms. In humans, saliva is rich in various AMPs that play a pivotal role in maintaining oral health by serving as the primary line of defense in the oral cavity. These peptides are essential for protection against a broad spectrum of pathogens, including bacteria and fungi. Recently, active research has been conducted on both naturally occurring AMPs and modified or synthetic AMPs for the treatment of oral pathogens and their application in dental materials.
Methods: We compiled previous studies on AMPs present in saliva and their target oral microorganisms. Additionally, we summarized research on artificially created AMPs targeting oral pathogens. Furthermore, we analyzed recent trends in applied studies, such as the development of oral rinses, toothpaste, and implant coatings using AMPs.
Results: Through a literature review, we identified 19 studies on AMPs present in the oral cavity and 40 studies testing AMPs derived from other organisms or synthetically engineered against oral pathogens. Additionally, we reviewed seven studies on the development of implant coatings and oral hygiene material additives using AMPs. These findings suggest the potential for discovering or developing AMPs with activity against specific oral pathogens that can be applied to improve oral health.
Conclusion: AMPs exhibit broad antimicrobial activity against a wide range of pathogens. Their mechanisms of action primarily involve attacking and disrupting the cell membranes of target microorganisms, making them effective against various pathogens. AMPs have the potential for use as coating materials for dental implants or restorative materials that require long-term use. Further research is needed to investigate the cytotoxicity, durability, and stability of AMPs in the oral environment to support their clinical use in dentistry.
Keywords : Antimicrobial peptides, Dental implants, Oral microbiome, Oral pathogen
Introduction

1. Background

Antimicrobial peptides (AMPs) are short sequences of amino acids, typically fewer than 50 amino acids, that exhibit strong antimicrobial activity against a wide range of microorganisms1). In the oral microbiome, AMPs are critical components of the innate immune system and serve as the first line of defense against harmful microorganisms2). Several AMPs, including histatins, defensins, and LL-37, have been found in the oral epithelium and saliva, and are considered key components of the oral defense system3-10). Additionally, these naturally occurring AMPs are host defense peptides that regulate the innate immune response of host cells and exhibit resistance to oral pathogenic microorganisms11). AMPs can be classified into various types based on their structure, such as alpha-helical, beta-sheet, looped, or extended peptides, with these structural characteristics closely related to their antimicrobial activity and mechanism of action12). Most AMPs are positively charged and possess amphipathic properties, indicating that they contain both hydrophilic and hydrophobic regions. This property is crucial for their interaction with microbial cell membranes12,13). These peptides exhibit broad-spectrum antimicrobial activity, allowing them to target a wide range of pathogenic microorganisms, including bacteria and fungi14). AMPs insert themselves into microbial membranes and form pores that disrupt membrane integrity, leading to cell lysis and death13,15). Some AMPs can penetrate microbial cells and interfere with critical processes such as DNA, RNA, or protein synthesis14,16-18).

The antimicrobial mechanism of AMPs begins with non-specific interactions with components of the bacterial membrane, such as negatively charged phospholipids, lipopolysaccharides, and teichoic acids19-21). When peptides are inserted into the lipid bilayer, the barrier function of the bacterial membrane is compromised, resulting in the loss of membrane potential, leakage of cytoplasmic components, and eventually cell death13,14,22,23). In addition to directly killing pathogens, AMPs can modulate immune responses by recruiting immune cells to infection sites and promoting the production of other immune molecules24).

The human body naturally produces AMPs in various parts of the oral cavity, including saliva, oral mucosa, and oral tissues25,26). These peptides are produced by various cells in the oral cavity, particularly epithelial cells, neutrophils, and salivary glands26,27). Key examples include defensins, cathelicidins (e.g., LL-37), histatins, calprotectin, and lactoferrin3-10,28-30). Defensins are essential AMPs in the oral cavity and are classified into α-defensins and β-defensins31). The α-defensins are primarily secreted by neutrophils and function to kill or inhibit bacteria, viruses, and fungi in the oral cavity3,31). β-Defensins are secreted by the oral mucosa and serve as a primary defense mechanism of the oral epithelial cells4-6,31). β-Defensin-2 and -3 are commonly found in the oral cavity and exhibit strong defense capabilities against not only bacteria but also some viruses4,5). Cathelicidin, also known as LL-37, is secreted by oral epithelial and white blood cells7). LL-37 exhibits antimicrobial activity against bacteria, viruses, and fungi found in the oral cavity. It also helps to regulate inflammation and promotes cell regeneration and tissue repair6-8).

Histidine-rich peptides (histatins) are mainly secreted by salivary glands9,10). Histatin-5 is a representative AMP with strong activity against fungi and plays a significant role in inhibiting oral fungal infections, such as Candida albicans10). In addition, histatins promote wound healing9). Calprotectin is an antimicrobial protein primarily secreted by white blood cells32). It inhibits bacterial and fungal growth by blocking metal ions28,32). This peptide exhibits antimicrobial activity, particularly against bacteria in the oral cavity28). Lactoferrin is a protein present in saliva that binds iron, preventing bacteria from utilizing it and thus inhibiting bacterial growth29,30). It is particularly effective against cavity-causing bacteria such as Streptococcus mutans29,30).

Some bacteria in the oral microbiome produce their own AMPs, known as bacteriocins, which help them compete with other microbial species33,34). AMPs selectively target pathogenic microorganisms, maintaining the balance of the oral microbiome while allowing beneficial (commensal) bacteria to thrive14,35). This selective action is crucial for preventing infections and preserving the beneficial microbial community that supports oral health35). When the balance of the oral microbiome is disrupted by poor oral hygiene, diet, or systemic health issues, the production and activity of AMPs can be altered28). This alteration can lead to the overgrowth of pathogenic bacteria, contributing to conditions such as gingivitis and periodontitis28,36). Owing to their potent antimicrobial properties and ability to modulate the immune response, synthetic AMPs are being studied for therapeutic use in the treatment of oral infections and diseases37). Synthetic or modified AMPs can be developed to enhance oral health by targeting specific pathogens without disturbing the overall microbiome37,38).

Synthetic or natural AMPs can be used in mouthwashes or dental treatments to prevent or treat infections38-40). The development of oral implant coatings and dental restoratives using AMPs represents an advanced biotechnological approach aimed at preventing infections and promoting oral health41). By applying these peptides to oral implants and dental restoratives, issues related to oral cavity infections can be effectively addressed41). Oral implants carry a risk of infection after surgery, and if an infection occurs, the risk of implant failure increases42). Coating implant surfaces with AMPs can help prevent post-implantation infections. AMPs have minimal side effects, increasing the biocompatibility of implants and helping to prevent periodontal diseases and other oral inflammations, thus improving implant success rates41).

Dental restoratives are used to repair decayed and damaged teeth. Using restoratives embedded with AMPs can inhibit bacterial growth around the restoration and prevent the recurrence of cavities43). The peptides combined with the restorative material can suppress bacteria such as S. mutans, the main cause of cavities, thus preventing cavity recurrence after treatment43). Some AMPs stimulate tissue regeneration, aiding the recovery of tissues surrounding the restored tooth and ensuring long-term oral health41,44,45). Restoratives containing AMPs resist microbial degradation, thereby prolonging the lifespan of the restorative material43).

AMPs are essential for oral health and act as natural antibiotics that help regulate microbial populations, prevent infections, and maintain a healthy balance within the oral microbiome2,13-18,46). The advantages of using AMPs as dental materials include their ability to act against various oral pathogens without causing resistance, even after long-term use38-41,43). However, disadvantages include the high cost of producing AMPs, concerns about how long these peptides can maintain their antimicrobial properties in dental environments, and how safely they degrade in the body41). Current research on implant coatings and dental restoratives using AMPs is actively progressing, with a focus on improving their stability and effectiveness41). AMPs are thought to offer a promising solution for peri-mucositis and peri-implantitis that may arise after dental implants and restorative treatments.

2. Objectives

This review summarizes research related to AMPs found in the oral cavity to understand their amino acid sequences and antimicrobial mechanisms. Additionally, it organizes previous studies on the use of synthetic AMPs to eliminate oral pathogens in tabular form. By analyzing these summarized results, this review explores the potential for utilizing synthetic AMPs, originally discovered outside the oral cavity, in oral care products, implant coatings, and dental restorative materials. The focus is on natural AMPs as alternative therapeutics for oral infections, such as dental cavities, thrush, and periodontitis. This review also examines both the current use of natural AMPs and the development of their synthetic counterparts for targeting oral pathogens.

Materials and Methods

1. Literature database search

A literature search was performed using PubMed (https://pubmed.ncbi.nlm.nih.gov/) and Google Scholar (https://scholar.google.com/). The keywords used for the search were “Antimicrobial peptide (against oral pathogens),” “Dental implant with peptide coating,” “Application of peptide in oral hygiene,” and related terms. Studies that were not focused on oral pathogens or oral hygiene, as well as those centered on antibiotics other than AMPs, were excluded. Following this selection process, a total of 66 articles were collected, and their content was analyzed and summarized.

2. Protein sequence of AMPs

The amino acid sequences of AMPs were retrieved from the NCBI (National Center for Biotechnology Information) database (https://www.ncbi.nlm.nih.gov/guide/proteins/) and UniProtKB (https://www.uniprot.org/).

Results and Discussion

1. The types and functions of AMPs present in the oral cavity

Various AMPs are secreted within the human oral environment (Table 1)3-10,28-30,47-54). Cystatins are natural inhibitors of cysteine proteinases and are found in various human tissues and body fluids55). Several studies have shown that cystatins possess antiviral and antibacterial properties. For instance, a tripeptide derivative of cystatin C has demonstrated antibacterial effects against group A streptococci, while phosphorylated rat cystatin α has been found to hinder the growth of Staphylococcus aureus56). Salivary cystatins suppress the growth of Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans47,48). Blancas-Luciano et al.49) demonstrated that cystatin C inhibited the growth of P. gingivalis without exhibiting cytotoxicity against human gingival fibroblasts.

Natural Antimicrobial Peptides in the Oral Cavity

Peptide name Origin Peptide sequence Target Reference
Alpha-defensins HNP 1-4 (α-defensins) Neutrophils, gingival sulcus, sites of inflammation, salivary duct cells HNP1 ACYCRIPACIAGERRYGTCIYQGRLWAFCC Candida albicans 3)
HNP2 CYCRIPACIAGERRYGTCIYQGRLWAFCC
HNP3 DCYCRIPACIAGERRYGTCIYQGRLWAFCC
HNP4 VCSCRLVFCRRTELRVGNCLIGGVSFAYCCTRV
Cystatins Human tissues, body fluids Cystatin C GGPMDASVEEEGVRRALDFAVGEYNKASNDMYHSRALQVVRARKQIVAGVNYFLDVELGRTTCTKTQPNLDNCPFHDQPHLKRKAFCSFQIYAVPWQGTMTLSKSTCQDA Porphyromonas gingivalis Aggregatibacter actinomycetemcomitans 47-49)
Cystatin SA MAWPLCTLLLLLATQAVALAWSPQEEDRIIEGGIYDADLNDERVQRALHFVISEYNKATEDEYYRRLLRVLRAREQIVGGVNYFFDIEVGRTICTKSQPNLDTCAFHEQPELQKKQLCSFQIYEVPWEDRMSLVNSRCQEA
Dhvar4a Salivary glands KRLFKKLLFSLRKY-NH2 Streptococcus mutans Streptococcus sobrinus 51)
LL-37 Neutrophils, gingival sulcus, salivary glands and ducts LLGDFFRKSKEKIGKEFKRIVQRIKDFLRNLVPRTES S. mutans Fusobacterium nucleatum A. actinomycetemcomitans P. gingivalis Capnocytophaga sputigena Staphylococcus aureus 6-8)
β-defensins: hBD1, hBD2, hBD3 Epithelia, salivary ducts hBD1 DHYNCVSSGGQCLYSACPIFTKIQGTCYRGKAKCCK hBD1: Poor antibacterial
hBD2, hBD3: S. mutans, Streptococcus sanguinis, F. nucleatum, P. gingivalis, C. albicans
4-6,50)
hBD2 PVTCLKSGAICHPVFCPRRYKQIGTCGLPGTKCCKKP
hBD3 GIINTLQKYYCRVRGGRCAVLSCLPKEEQIGKCSTRGRKCCRRKK
Histatins Salivary glands/ducts HTN1 MKFFVFALVLALMISMISADSHEKRHHGYRRKFHEKHHSHREFPFYGDYGSNYLYDN C. albicans S. mutans 9,10)
HTN3 MKFFVFALILALMLSMTGADSHAKRHHGYKRKFHEKHHSHRGYRSNYLYDN
HTN5 DSHAKRHHGYKRKFHEKHHSHRGY
Adrenomedullin Epithelium YRQSMNNFQGLRSFGCRFGTCTVQKLAHQIYQFTDKDKDNVAPRSKISPQGY-NH2 P. gingivalis S. mutans 52)
Azurocidin Neutrophil NQGRHFCGGALIHARFVMTAASCFQ Gram-negative bacteria, Enterococcus hirae (previously known as Streptococcus faecalis ATCC8043) 53)
Calprotectin Neutrophils, monocytes, macrophages, mucosal keratinocytes Calprotectin A MLTELEKALNSIIDVYHKYSLIKGNFHAVYRDDLKKLLETESPQYIRKKGADVWFKELDINTDGAVNFQEFLILVIKMGVAAHKKSHEESHKE
P. gingivalis 28)
Calprotectin B TSKMSQLERNIETIINTFHQYSVKLGHPDTLNQGEFKELVRKDLQNFLKKENKNEKVIEHIMEDLDTNADKQLSFEEFIMLMARLTWASHEKMHEGDEGPGHHHKPGLGEGTP
Lactoferrin Acinar cells GRRRSVQWCAVSNPEATKCFQWQRNMRKVRGPPVSCIKRDSPIQCIQAIAENRADAVTLDGGFIYEAGLAPYKLRPVAAEVYGTERQPRTHYYAVAVVKKGGSFQLNELQGLKSCHTGLRRTAGWNVPIGTLRPFLNWTGPPEPIEAAVARFFSASCVPGADKGQFPNLCRLCAGTGENKCAFSSQEPYFSYSGAFKCLKDGAGDVAFIRESTVFEDLSDEAERDEYELLCPDNTRKPVDKFKDCHLARVPSHAVVARSVNGKEDAIWNLLRQAQEKFGKDKSPKFQLFGSPSGQKDLLFKDSAIGFSRVPPRIDSGLYLGSGYFTAIQNLRKSEEEVAARRARVVWCAVGEQELRKCNQWSGLSEGSVTCSSASTTEDCIALVLKGEADAMSLDGGYVYTAGKCGLVPVLAENYKSAQSSDPDPNCVDRPVEGYLAVAVVRRSDTSLTWNSVKGKKSCHTAVDRTAGWNIPMGLLFNQTGSCKFDEYFSQSCAPGSDPASNLCALCIGDEEGENKCVPNSNERYYGYTGAFRCLAENAGDVAFVKDVTVLQNTDGNNNEAWAKDLKLADFALLCLDGKRKPVTEARSCHLAMAPNHAVVSRMDKVERLKQVLLHQQAKFGRNGSDCPDKFCLFQSETKNLLFNDNTECLARLHGKTTYEKYLGPQYVAGITNLKKCSTSPLLEACEFLRK P. gingivalis, Prevotella intermedia, S. mutans, Candida species 29,30,54)

hBD: human β-defensin-3.



Human β-defensin-3 (hBD3) is a natural AMP composed of 45 amino acids, with broad-spectrum activity against bacteria and fungi4-6). Ahn et al.50) investigated the effects of the C-terminal 15 amino acids of hBD3 (hBD3-C15) on S. mutans biofilm formation. hBD3-C15 inhibits bacterial growth, displays bactericidal activity, and reduces biofilm formation in a dose-dependent manner. Additionally, hBD3-C15 enhances the antimicrobial and antibiofilm effects of calcium hydroxide and chlorhexidine digluconate, which are commonly used dental disinfectants. hBD3-C15 also inhibits biofilm formation of S. mutans, Enterococcus faecalis, and Streptococcus gordonii on human dental slices, demonstrating its potential against dental caries and endodontic infections50).

2. Inhibition of oral pathogens’ growth using AMPs produced by other organisms or artificial synthetic AMPs

Various modified synthetic AMPs have been developed using natural AMP templates by incorporating different charges, hydrophobicity, chain lengths, amino acid sequences, and amphipathicity57,58). Recently, research has focused on utilizing AMPs produced by other organisms to eliminate oral pathogens. Additionally, efforts are being made to use synthetically designed AMPs to treat oral pathogens. Consequently, researchers are developing synthetic AMPs with promising stability and biocompatibility. Therefore, synthetic AMPs have the potential to serve as alternatives to traditional antimicrobial therapy59).

To design effective synthetic AMPs, understanding the structure-function relationship of AMPs is essential60). The hydrophobicity of AMPs is a critical factor in their ability to permeabilize cell membranes, and the arrangement of hydrophobic regions is crucial for linking AMP structures to their activity60,61). Amphiphilicity, which refers to the presence of distinct polar and nonpolar regions, is key to antimicrobial activity62). Charge is another significant characteristic that affects the activity of cationic AMPs63). Through non-specific electrostatic interactions, positively charged residues bind to the anionic head groups of membrane phospholipids63). Many AMPs are rich in cationic amino acids such as arginine and lysine64). Additionally, positively charged residues near the carboxy-terminus can aid AMP insertion into the outer membrane surface63,64). Specifically, arginine residues are associated with increased membrane insertion and translocation compared with lysine or histidine, partly because of the ability of guanidinium groups to form hydrogen bonds with the hydrophobic core of the lipid bilayer65). The insertion of AMPs into the inner core of the membrane lipid bilayer is heavily influenced by hydrophobic interactions between residues such as proline and tryptophan and hydrocarbon phospholipid tails66). The hydrophobicity of a peptide is directly correlated with its activity60). The secondary structure of AMPs depends on interactions in the peptide backbone, as well as partitioning-folding coupling67). AMPs are disordered in aqueous solutions and typically adopt an α-helical or folded conformation (containing antiparallel β-sheets) in membrane-mimetic environments67,68).

The mechanisms of action of AMPs are concentration-dependent69). Various models have been proposed to describe transmembrane pore formation. The barrel-stave model is based on the interaction of the hydrophobic region of the peptide with the hydrocarbon core of the lipid bilayer70). In contrast, the toroidal model is formed through the interaction between the hydrophilic region of the peptide and the charged phospholipid heads on the membrane surface70). The carpet model is associated with the disruption of the cell membrane through micelle formation and is observed to be concentration-dependent4). Membrane depolarization describes the process of electroporation, in which pores are formed by changes in the external electric field of the membrane70,71). This amphipathic structure is crucial for AMPs to penetrate membranes and form hydrophobic channels or pores12,58,72,73). Amphipathic AMPs attack membranes by interacting with hydrophobic lipids73).

Step 1: Cationic AMPs bind to the negatively charged surfaces of gram-negative (outer membrane) or gram-positive (cell wall) bacteria14,15,74,75). Step 2: AMPs accumulate on the bacterial membrane surface and adopt a stable secondary structure14,75,76). Step 3: As the peptide-to-lipid ratio on the bacterial membrane increases, the AMP hydrophobic region gradually interacts with the phospholipid heads of the bacterial membrane75,76). Step 4: When AMPs reach a threshold concentration, they disrupt the bacterial membrane, causing cell lysis14,15,74-76). However, AMPs may also act intracellularly by inhibiting DNA, RNA, or protein synthesis14,77,78).

Strategies to enhance antimicrobial activity include the design of novel AMPs79,80). The rational design of novel AMPs aims to elucidate the mechanisms of action, such as the extent of membrane disruption, and to explore the relationship between the structural elements of the peptide and its activity81,82). This is particularly important given the occasional need for high concentrations in natural forms and the relative cost of solid-phase peptide synthesis79,82,83). Common synthetic strategies include: 1. cyclization of linear regions; 2. D-amino acid substitution to evade protease recognition and subsequent degradation; and 3. replacement of hydrophobic residues to study the effects of hydrophobicity and amphiphilicity on cytotoxicity58,83). Stability and cytotoxicity are two important issues related to the design of synthetic AMPs for medical applications84). First, it is crucial to protect AMPs from proteases in biological systems85). Various approaches include the insertion of artificial amino acids, cyclization, modified amino and/or carboxyl terminals, non-peptidic backbones (peptidomimetics), and multimerized AMPs38,58,59,86). Although AMPs can non-selectively kill bacteria, selective killing of specific bacteria, such as S. mutans, is feasible by creating a specific competence-stimulating peptide for S. mutans.

We have compiled and reviewed AMPs, including synthetic AMPs, that target oral pathogens but are derived from sources outside the oral environment (Table 2)51,80,87-113). Below are notable examples. Franzman et al.87) conjugated sheep myeloid AMP (SMAP) 28 with rabbit immunoglobulin G (IgG) to demonstrate its antibacterial effect against specific bacteria. Their study showed that the IgG-SMAP28 conjugate exhibited concentration-dependent specificity for P. gingivalis in a solution containing P. gingivalis, A. actinomycetemcomitans, and Peptostreptococcus micros87). This finding suggests the potential for developing antibiotics that target specific oral pathogens, reducing side effects associated with broad-spectrum antibiotics.

Antimicrobial Peptides with Antibiotic Activity Against Oral Pathogens

Peptide name Origin Peptide sequence Target References
IgG-SMAP28 Conjugation between SMAP and rabbit IgG SMAP28 RGLRRLGRKIAHGVKKYGPTVLRIIRIA- NH2 Porphyromonas gingivalis 87)
KSL Synthetic peptide KKVVFKVKFK-NH2 Streptococcus mutans 80,88)
D-Nal-Pac-525 Synthetic peptide Ac-K-Nal-RR-Nal-VR-Nal-I-NH2 Nal=β-naphthylalanines Streptococcus gordonii 89)
Nal-P-113 Synthetic peptide AKR-Nal-Nal-GYKRKF-Nal S. gordonii Fusobacterium nucleatum P. gingivalis 90)
Pep-7 Synthetic peptide RPHGAGEGIDRVPAGP-SPSEVGLAIPSGK P. gingivalis 91)
GH12 Synthetic peptide GLLWHLLHHLLH-NH2 S. mutans Streptococcus salivarius Streptococcus sobrinus 92)
ZXR-2 Synthetic peptide FKIGGFIKKLWRSLLA S. mutans 93)
DP7 Synthetic peptide VQWRIRVAVIRK-NH2 P. gingivalis 100)
PLNC8 αβ Lactobacillus plantarum PLNC8α DLTTKLWSSWGYYLGKKARWNLKHPYVQF P. gingivalis 94,95)
PLNC8β SVPTSVYTLGIKILWSAYKHRKTIEKSFNKGFYH
AmyI-1-18 Oryza sativa AAPDIDHLNKRVQRELIG F. nucleatum P. gingivalis 96,97)
LF-1 Synthetic peptide (derived from lactotransferrin) WKLLRKAWKLLRKA S. mutans 99)
K4-S4(1-15)a Frog skin LWKTLLKKVLKAAA-NH2 S. mutans 51)
C16G2 Synthetic peptide TFFRLFNRSFTQALGKGGGKNLRIIRKGIHIIKKY-NH2 Streptococcus species, although this was specifically designed to target S. mutans 101)
Temporin-GHa Frog hylarana guentheri FLQHIIGALGHLF S. mutans 102)
GHaR Frog hylarana guentheri FLQRIIGALGRLF S. mutans 102)
GHa11R Frog hylarana guentheri FLQHIIGALGRLF S. mutans 102)
Active casein antimicrobial peptide mixture (CAMPs) Milk casein β-lactoglobulin (41∼56) AASDISLLDAQSAPLR S. mutans, P. gingivalis 103)
β-lactoglobulin (141∼151) TPEVDDEALEK
β-casein (113∼120) VKEAMAPK
β-casein (121∼128) HKEMPFPK
β-casein (208∼224) YQEPVLGPVRGPFPIIV
α-s1-casein (16∼39) RPKHPIKHQGLPQEVLNENLLRFF
α-s1-casein (30∼37) VLNENLLR
α-s1-casein (110∼119) LEQLLRLKKY
α-s2-casein (163∼176) TKKTKLTEEEKNRL
α-s2-casein (213∼222) TKVIPYVRYL
κ-casein (63∼70) YYQQKPVA
Tet213 Synthetic peptide KRWWKWWRRC Staphylococcus aureus, Pseudomonas aeruginosa 104,105)
Magainins Frog (Xenopus laevis) skin secretions 1 GIGKFLHSAGKFGKAFVGEIMKS P. gingivalis 106)
2 GIGKFLHSAKKFGKAFVGEIMNS
Nisin Lactococcus lactis ITSISLCTPGCKTGALMGCNMKTATCHCSIHVSK MRSA 107)
Melittin Bee and wasp venoms GIGAVLKVLTTGLPALISWIKRKRQQ-NH2 MRSA, VRE 108-110)
Apamin Bee and wasp venoms CNCKAPETALCARRCQQH-NH2 MRSA 108,109)
Mastoparan Bee and wasp venoms INLKALAALAKKIL-NH2 MRSA 108,111)
Pleurocidin Pleuronectes americanusskin secretions GWGSFFKKAAHVGKHVGKAALTHYL Streptococcus species 112)
Neurokinin A Excitatory neurons HKTDSFVGLM S. mutans, L. acidophilus, E. faecalis, E. coli, S. aureus, P. aeruginosa, C. albicans 113)
Neuropeptide Y Excitatory neurons YPSKPDNPGEDAPAEDLARYYSALRHYITRQRY 113)
Neuropeptides substance P Excitatory neurons RPKPQQFFGLM 113)
Calcitonin gene-related peptide Excitatory neurons ACDTATCVTHRLAGLLSRSGGVVKNNFVPTNVGSKAF 113)


Hong et al.80) developed the antimicrobial decapeptide KSL, which exhibited broad antimicrobial activity against diverse enteric bacteria. Liu et al.88) evaluated the antimicrobial activity of KSL against S. mutans and C. albicans, focusing on S. mutans. The results showed that KSL effectively inhibited the growth of various oral bacteria and fungi, with S. mutans and Lactobacillus acidophilus being the most susceptible88). Their study also demonstrated that KSL inhibits biofilm formation and reduces pre-formed biofilms88,114).

Li et al.89) designed three synthetic peptides and evaluated their effects on the growth of S. mutans and biofilm formation. Among the three peptides, D-Nal-Pac-525 showed strong antimicrobial activity against S. mutans, with a minimum inhibitory concentration (MIC) of 4 μg/ml and inhibition of biofilm formation at 2 μg/ml89).

Wang et al.90) revealed a novel role for the synthetic cationic AMP Nal-P-113, which demonstrated potent efficacy against periodontal pathogens, including S. gordonii, Fusobacterium nucleatum, and P. gingivalis, representing early, middle, and late colonizers of dental plaque biofilms. Nal-P-113 not only inhibits planktonic bacteria and biofilm formation but also effectively eradicates polymicrobial biofilms. They confirmed that Nal-P-113 perforated bacterial membranes, leading to cell death and biofilm disintegration90).

Suwandecha et al.91) developed an AMP named Pep-7 specifically designed to combat P. gingivalis. Pep-7 was designed to be sufficiently short to compensate for the longer lengths of traditional AMPs used to treat P. gingivalis. In their study, Pep-7 demonstrated potent antimicrobial activity against two pathogenic strains of P. gingivalis by inducing pore formation at the poles of P. gingivalis cytoplasmic membranes91). Pep-7 was non-toxic to periodontal cells over a broad range of concentrations (4.4 to 70.8 μM) and displayed heat stability under autoclave conditions with activity across a pH range of 6.8∼8.591).

Tu et al.92) investigated the antimicrobial activity of the synthetic amphipathic α-helical peptide GH12 against oral streptococci in vitro. GH12 exhibited potent bactericidal activity, with MICs ranging from 6.7 to 32.0 μg/ml92). GH12 effectively inhibits biofilm formation and reduces the metabolic activity of mature biofilms, particularly in S. mutans, S. sobrinus, and Streptococcus salivarius92).

ZXR-2, a synthetic peptide designed by Chen et al.93), shows a broad range of antibacterial activity against a variety of gram-positive and gram-negative oral pathogens, including S. mutans. ZXR-2 inhibits bacterial cell growth and the formation of S. mutans biofilms by disrupting bacterial cell membranes93). The most notable advantage of ZXR-2 is its ability to eliminate bacterial cells rapidly. According to a study by Chen et al.93), a time-course killing assay demonstrated that treatment with ZXR-2 at 4×MIC resulted in the death of most bacterial cells within 5 minutes. Furthermore, even at the MIC, ZXR-2 exhibited a limited hemolytic effect of less than 15%93).

Khalaf et al.95) showed that two strains of Lactobacillus plantarum inhibit the growth of P. gingivalis. The bacteriocin PLNC8 αβ from L. plantarum was effective, binding to P. gingivalis membranes and causing rapid permeabilization94,95). They concluded in their study that both soluble and immobilized forms of PLNC8 αβ may be used to prevent P. gingivalis colonization, complementing the host immune system in defending against periodontitis-associated pathogens94,95).

AmyI-1-18 is a cationic α-helical peptide derived from rice (Oryza sativa)96). Taniguchi et al.96) synthesized 12 analogs of AmyI-1-18 to enhance antibacterial activity. Among the analogs, AmyI-1-18 (N3L) showed the highest antibacterial activity and low hemolytic activity96). Matsugishi et al.97) synthesized an analog of AmyI-1-18, G12R, which inhibits biofilm formation by P. gingivalis and F. nucleatum. It showed significant bactericidal activity, particularly against F. nucleatum97).

Liang et al.98) constructed a short linear peptide, LR-10, inspired by reutericin 6 and gassericin A, which are produced by various commensal bacteria in the oral cavity. Antibacterial assays showed that LR-10 exhibited potent activity against S. mutans (MIC: 3.3 μM) without inducing resistance and was effective under physiological conditions98). LR-10 also demonstrated a higher bactericidal rate than either chlorhexidine or erythromycin. Additionally, LR-10 effectively inhibited biofilm formation and killed biofilm-encased S. mutans at low concentrations (6.5 μM). Hemolytic activity and cytotoxicity tests confirmed that LR-10 maintained its biocompatibility at effective concentrations98).

Feng et al.99) designed LF-1, a synthetic AMP derived from the lactotransferrin functional domain. LF-1 exhibited selective activity against S. mutans with a MIC of 8 μmol/L and altered the membrane potential and hydrophobicity of S. mutans by forming mesosome-like structures on their membrane99).

Various in vivo studies have demonstrated that combining AMPs with conventional antibiotics can result in a synergistic effect115). However, studies specifically targeting oral pathogens remain limited. Fernandes et al.54) showed that co-administering the AMP lactoferrin with the antibiotic amphotericin B exhibited synergistic antifungal activity against Candida species. Similarly, Lobos et al.116) demonstrated in their in vitro study that the combination of the AMP bacteriocin PsVP-10 with antibiotics chlorhexidine and triclosan produced synergistic antimicrobial effects against S. mutans and S. sobrinus.

3. Application of AMPs in dental materials

Synthetic AMPs represent a potential therapeutic strategy for managing oral diseases59). The increase in antibiotic-resistant bacteria due to the overuse and misuse of antibiotics is a significant concern117). Therefore, new approaches are needed to combat antibiotic-resistant bacterial infections. AMPs are promising candidates for the treatment of oral infections13,118). Despite progress over the past 40 years, only a few AMPs have been approved for clinical use13). Several studies have utilized AMPs in antimicrobial mouthwashes, antimicrobial coatings for implants, and dental restorative materials. Because AMPs do not induce antibiotic resistance even with long-term use, they are suitable as coating materials for implants and dental restorative materials119). Recent studies have shown that cationic AMPs are a promising family of antibacterial agents active against oral pathogenic bacteria with a lower propensity for the development of antimicrobial resistance61,64,96,120).

In the context of the oral microbiome, AMPs can target bacteria involved in biofilm formation and have potential applications in the treatment of chronic periodontitis36). Additionally, native oral AMPs can have immunomodulatory effects, making their application potentially useful for controlling dysbiosis and inflammation associated with pathogenic bacteria in the oral microbiome121-123). AMPs originate from a variety of hosts and are diverse in structure and function, with the ability to modify their amino acid composition for broad-spectrum applications as well as targeting specific pathogens84).

Peri-implantitis, an inflammatory condition affecting the hard and soft tissues surrounding dental implants, is the leading cause of implant failure, with a prevalence rate ranging from 28% to 56%124,125). The primary factor contributing to implant failure is microbial infection caused by various oral pathogens. Current treatment approaches, such as laser therapy, surgical resection, and regenerative procedures, have shown limited efficacy126,127). The difficulty in removing plaque from an implant’s rough, threaded surface has led to a growing interest in preventive strategies focused on reducing plaque formation127).

Various physical and chemical strategies have been developed for antimicrobial coatings to enhance biointegration and minimize bacterial adherence to implant materials and subsequent infection. These include organic coatings such as polymers and biomimetic films, as well as inorganic coatings such as titanium oxide128). Among these diverse coating materials, AMPs have attracted significant research interest due to their broad-spectrum antimicrobial activity and multimodal mechanisms of action41). Accordingly, various AMPs have been studied as coating materials for dental implants (see examples in Table 339,40,45,101,104,105,129,130), Fig. 1).

Fig. 1. Examples of peptides used as coating materials for dental implants. Peptides exhibiting antimicrobial activity, as well as promoting anti-inflammatory effects, osseointegration, and bioadhesion, are actively being investigated as potential coating materials for dental implants.

Application Examples of Antimicrobial Peptides in Oral Health and Hygiene

Peptide name Application Description References
Lactoperoxidase Toothpaste, mouthwash, and gel Used as a saliva substitute and showed improvement of xerostomic symptoms and reduction of streptococci 39)
GERM CLEAN Oral spray Oral spray containing GERM CLEAN showed an inhibitory effect on the initial adhesion, acid production, extracellular polysaccharides production, and biofilm formation of Streptococcus mutans 40)
C16G2 Oral rinse C16G2 oral rinse showed a decrease in plaque, salivary S. mutans, lactic acid production, and enamel demineralization 101)
Tet213 Dental implant coating CaP-Tet213 and CaP-HHC36 coating showed antimicrobial activity against Staphylococcus aureus and Pseudomonas aeruginosa 104,105)
HHC36
β-defensin-2 Coated recombinant human β-defensin-2 on titanium surfaces yielded antimicrobial activities and prevented bacterial colonization 129)
Human β-defensin-3 containing chimeric peptides Chimeric peptide containing human β-defensing-3 coating prevented biofilm formation by inhibition of initial colonizing Streptococci 130)
LL-37 Nanopore coating loaded with LL-37 showed diverse antibacterial and osteogenic induction abilities 45)


4. Conclusion and suggestions

In this review, we investigated the AMPs known to exist in the oral environment and examined the amino acid sequences of synthetic AMPs developed in previous studies targeting oral pathogens. For applications in oral health, AMPs offer clear advantages, as well as challenges that must be addressed. Due to their broad-spectrum activity and low risk of inducing bacterial resistance, AMPs are emerging as promising materials for oral hygiene119,124,125). However, natural AMPs are susceptible to proteases, and compared to small-molecule drugs, AMPs are relatively large and require high concentrations to be effective12,69). Therefore, derivatives based on natural AMPs that exhibit strong antimicrobial activity at low concentrations and resistance to proteolysis need to be developed. Additionally, there is potential for combining newly designed AMPs with traditional antibiotics to create powerful antimicrobial agents.

In the field of dental materials, research on developing implant coatings using not only AMPs but also other functional peptides is actively underway. This includes the development of peptides that enhance osseointegration and improve implant adhesion (Fig. 1).

However, no consensus has yet been reached on the most suitable peptide for dental implant coatings41). This lack of agreement stems from the limited research providing clear evidence on the durability of AMP coatings on implant surfaces and their stability in the oral environment. Future studies addressing these issues are anticipated to position AMPs as a groundbreaking solution for preventing diseases caused by oral pathogens.

Acknowledgements

None.

Notes

Conflict of interest

No potential conflict of interest relevant to this article was reported.

Ethical approval

Not applicable.

Author contributions

Conceptualization: Youn-Soo Shim and Jun Hyuck Lee. Data acquisition: Sehyeok Im. Formal analysis: Sehyeok Im. Funding: Jun Hyuck Lee. Supervision: Youn-Soo Shim and Jun Hyuck Lee. Writing-original draft: Sehyeok Im. Writing-review & editing: Youn-Soo Shim and Jun Hyuck Lee.

Funding

This research was supported by the project titled “Development of potential antibiotic compounds using polar organism resources (20200610, KOPRI Grant PM24030),” funded by the Ministry of Oceans and Fisheries, Korea.

Data availability

Raw data will be provided by the corresponding author upon reasonable request.

References
  1. Ageitos JM, Sánchez-Pérez A, Calo-Mata P, Villa TG: Antimicrobial peptides (AMPs): ancient compounds that represent novel weapons in the fight against bacteria. Biochem Pharmacol 133: 117-138, 2017. https://doi.org/10.1016/j.bcp.2016.09.018
    Pubmed CrossRef
  2. Grant M, Kilsgård O, Åkerman S, et al: The human salivary antimicrobial peptide profile according to the oral microbiota in health, periodontitis and smoking. J Innate Immun 11: 432-444, 2018. https://doi.org/10.1159/000494146
    Pubmed KoreaMed CrossRef
  3. Raj PA, Antonyraj KJ, Karunakaran T: Large-scale synthesis and functional elements for the antimicrobial activity of defensins. Biochem J 347: 633-641, 2000. https://doi.org/10.1042/bj3470633
    Pubmed KoreaMed CrossRef
  4. Joly S, Maze C, McCray PB, Guthmiller JM: Human β-defensins 2 and 3 demonstrate strain-selective activity against oral microorganisms. J Clin Microbiol 42: 1024-1029, 2004. https://doi.org/10.1128/jcm.42.3.1024-1029.2004
    Pubmed KoreaMed CrossRef
  5. Maisetta G, Batoni G, Esin S, et al: Activity of human β- defensin 3 alone or combined with other antimicrobial agents against oral bacteria. Antimicrob Agents Chemother 47: 3349-3351, 2003. https://doi.org/10.1128/aac.47.10.3349-3351.2003
    Pubmed KoreaMed CrossRef
  6. Ouhara K, Komatsuzawa H, Yamada S, et al: Susceptibilities of periodontopathogenic and cariogenic bacteria to antibacterial peptides, β-defensins and LL37, produced by human epithelial cells. J Antimicrob Chemother 55: 888-896, 2005. https://doi.org/10.1093/jac/dki103
    KoreaMed CrossRef
  7. Inomata M, Into T, Murakami Y: Suppressive effect of the antimicrobial peptide LL-37 on expression of IL-6, IL-8 and CXCL10 induced by Porphyromonas gingivalis cells and extracts in human gingival fibroblasts. Eur J Oral Sci 118: 574-581, 2010. https://doi.org/10.1111/j.1600-0722.2010.00775.x
    Pubmed CrossRef
  8. Tanaka D, Miyasaki KT, Lehrer RI: Sensitivity of Actinobacillus actinomycetemcomitans and Capnocytophaga spp. to the bactericidal action of LL-37: a cathelicidin found in human leukocytes and epithelium. Oral Microbiol Immunol 15: 226-231, 2000. https://doi.org/10.1034/j.1399-302x.2000.150403.x
    Pubmed CrossRef
  9. Oppenheim FG, Xu T, McMillian FM, et al: Histatins, a novel family of histidine-rich proteins in human parotid secretion. Isolation, characterization, primary structure, and fungistatic effects on Candida albicans. J Biol Chem 263: 7472-7477, 1988. https://doi.org/10.1016/s0021-9258(18)68522-9
    Pubmed CrossRef
  10. Fernández-Presas AM, Márquez Torres Y, García González R, et al: Ultrastructural damage in Streptococcus mutans incubated with saliva and histatin 5. Arch Oral Biol 87: 226-234, 2018. https://doi.org/10.1016/j.archoralbio.2018.01.004
    Pubmed CrossRef
  11. Overhage J, Campisano A, Bains M, Torfs ECW, Rehm BHA, Hancock REW: Human host defense peptide LL-37 prevents bacterial biofilm formation. Infect Immun 76: 4176-4182, 2008. https://doi.org/10.1128/iai.00318-08
    Pubmed KoreaMed CrossRef
  12. Huan Y, Kong Q, Mou H, Yi H: Antimicrobial peptides: classification, design, application and research progress in multiple fields. Front Microbiol 11: 582779, 2020. https://doi.org/10.3389/fmicb.2020.582779
    Pubmed KoreaMed CrossRef
  13. Shai Y: Mode of action of membrane active antimicrobial peptides. Pept Sci 66: 236-248, 2002. https://doi.org/10.1002/bip.10260
    Pubmed CrossRef
  14. Yeaman MR, Yount NY: Mechanisms of antimicrobial peptide action and resistance. Pharmacol Rev 55: 27-55, 2003. https://doi.org/10.1124/pr.55.1.2
    Pubmed CrossRef
  15. Sato H, Feix JB: Peptide-membrane interactions and mechanisms of membrane destruction by amphipathic α-helical antimicrobial peptides. Biochim Biophys Acta 1758: 1245-1256, 2006. https://doi.org/10.1016/j.bbamem.2006.02.021
    Pubmed CrossRef
  16. Bahar AA, Ren D: Antimicrobial peptides. Pharmaceuticals 6: 1543-1575, 2013. https://doi.org/10.3390/ph6121543
    Pubmed KoreaMed CrossRef
  17. Mardirossian M, Grzela R, Giglione C, et al: The host antimicrobial peptide Bac71-35 binds to bacterial ribosomal proteins and inhibits protein synthesis. Chem Biol 21: 1639-1647, 2014. https://doi.org/10.1016/j.chembiol.2014.10.009
    Pubmed CrossRef
  18. Graf M, Mardirossian M, Nguyen F, et al: Proline-rich antimicrobial peptides targeting protein synthesis. Nat Prod Rep 34: 702-711, 2017. https://doi.org/10.1039/C7NP00020K
    Pubmed CrossRef
  19. Travkova OG, Moehwald H, Brezesinski G: The interaction of antimicrobial peptides with membranes. Adv Colloid Interface Sci 247: 521-532, 2017. https://doi.org/10.1016/j.cis.2017.06.001
    Pubmed CrossRef
  20. Wei L, Yang J, He X, et al: Structure and function of a potent lipopolysaccharide-binding antimicrobial and anti-inflammatory peptide. J Med Chem 56: 3546-3556, 2013. https://doi.org/10.1021/jm4004158
    Pubmed CrossRef
  21. Malanovic N, Lohner K: Antimicrobial peptides targeting gram-positive bacteria. Pharmaceuticals (Basel) 9: 59, 2016. https://doi.org/10.3390/ph9030059
    Pubmed KoreaMed CrossRef
  22. Epand RM, Epand RF: Bacterial membrane lipids in the action of antimicrobial agents. J Pept Sci 17: 298-305, 2011. https://doi.org/10.1002/psc.1319
    Pubmed CrossRef
  23. Faust JE, Yang PY, Huang HW: Action of antimicrobial peptides on bacterial and lipid membranes: a direct comparison. Biophys J 112: 1663-1672, 2017. https://doi.org/10.1016/j.bpj.2017.03.003
    Pubmed KoreaMed CrossRef
  24. Scott MG, Davidson DJ, Gold MR, Bowdish D, Hancock RE: The human antimicrobial peptide LL-37 is a multifunctional modulator of innate immune responses. J Immunol 169: 3883-3891, 2002. https://doi.org/10.4049/jimmunol.169.7.3883
    Pubmed CrossRef
  25. Wiesner J, Vilcinskas A: Antimicrobial peptides: the ancient arm of the human immune system. Virulence 1: 440-464, 2010. https://doi.org/10.4161/viru.1.5.12983
    Pubmed CrossRef
  26. Bastos P, Trindade F, da Costa J, Ferreira R, Vitorino R: Human antimicrobial peptides in bodily fluids: current knowledge and therapeutic perspectives in the postantibiotic era. Med Res Rev 38: 101-146, 2018. https://doi.org/10.1002/med.21435
    Pubmed KoreaMed CrossRef
  27. Wang G: Human antimicrobial peptides and proteins. Pharmaceuticals 7: 545-594, 2014. https://doi.org/10.3390/ph7050545
    Pubmed KoreaMed CrossRef
  28. Dale BA, Fredericks LP: Antimicrobial peptides in the oral environment: expression and function in health and disease. Curr Issues Mol Biol 7: 119-133, 2005. https://doi.org/10.1093/jac/dki103
    KoreaMed CrossRef
  29. Wakabayashi H, Yamauchi K, Kobayashi T, Yaeshima T, Iwatsuki K, Yoshie H: Inhibitory effects of lactoferrin on growth and biofilm formation of Porphyromonas gingivalis and Prevotella intermedia. Antimicrob Agents Chemother 53: 3308-3316, 2009. https://doi.org/10.1128/aac.01688-08
    Pubmed KoreaMed CrossRef
  30. Velusamy S, Markowitz K, Fine D, Velliyagounder K: Human lactoferrin protects against Streptococcus mutans-induced caries in mice. Oral Dis 22: 148-154, 2016. https://doi.org/10.1111/odi.12401
    Pubmed CrossRef
  31. Schneider JJ, Unholzer A, Schaller M, Schäfer-Korting M, Korting HC: Human defensins. J Mol Med (Berl) 83: 587-595, 2005. https://doi.org/10.1007/s00109-005-0657-1
    Pubmed CrossRef
  32. Jukic A, Bakiri L, Wagner EF, Tilg H, Adolph TE: Calprotectin: from biomarker to biological function. Gut 70: 1978-1988, 2021. https://doi.org/10.1136/gutjnl-2021-324855
    Pubmed KoreaMed CrossRef
  33. Wang BY, Kuramitsu Howard K: Interactions between oral bacteria: inhibition of Streptococcus mutans bacteriocin production by Streptococcus gordonii. Appl Environ Microbiol 71: 354-362, 2005. https://doi.org/10.1128/AEM.71.1.354-362.2005
    Pubmed KoreaMed CrossRef
  34. Santagati M, Scillato M, Patanè F, Aiello C, Stefani S: Bacteriocin-producing oral streptococci and inhibition of respiratory pathogens. FEMS Immunol Med Microbiol 65: 23-31, 2012. https://doi.org/10.1111/j.1574-695X.2012.00928.x
    Pubmed CrossRef
  35. Matsuzaki K: Control of cell selectivity of antimicrobial peptides. Biochim Biophys Acta 1788: 1687-1692, 2009. https://doi.org/10.1016/j.bbamem.2008.09.013
    Pubmed CrossRef
  36. Gorr SU, Abdolhosseini M: Antimicrobial peptides and periodontal disease. J Clin Periodontol 38 Suppl 11: 126-141, 2011. https://doi.org/10.1111/j.1600-051X.2010.01664.x
    Pubmed CrossRef
  37. Niu JY, Yin IX, Mei ML, Wu WKK, Li QL, Chu CH: The multifaceted roles of antimicrobial peptides in oral diseases. Mol Oral Microbiol 36: 159-171, 2021. https://doi.org/10.1111/omi.12333
    Pubmed CrossRef
  38. Luong AD, Buzid A, Luong JHT: Important roles and potential uses of natural and synthetic antimicrobial peptides (AMPs) in oral diseases: cavity, periodontal disease, and thrush. J Funct Biomater 13: 175, 2022. https://doi.org/10.3390/jfb13040175
    Pubmed KoreaMed CrossRef
  39. Artym J, Zimecki M: Milk-derived proteins and peptides in clinical trials. Postepy Hig Med Dosw (Online) 67: 800-816, 2013. https://doi.org/10.5604/17322693.1061635
    Pubmed CrossRef
  40. Xiong K, Chen X, Hu H, Hou H, Gao P, Zou L: Antimicrobial effect of a peptide containing novel oral spray on Streptococcus mutans. Biomed Res Int 2020: 6853652, 2020. https://doi.org/10.1155/2020/6853652
    Pubmed KoreaMed CrossRef
  41. Sun Z, Ma L, Sun X, Sloan AJ, O'Brien-Simpson NM, Li W: The overview of antimicrobial peptide-coated implants against oral bacterial infections. Aggregate 4: e309, 2023. https://doi.org/10.1002/agt2.309
    CrossRef
  42. Derks J, Tomasi C: Peri-implant health and disease. A systematic review of current epidemiology. J Clin Periodontol 42: S158-S171, 2015. https://doi.org/10.1111/jcpe.12334
    CrossRef
  43. Xie SX, Song L, Yuca E, et al: Antimicrobial peptide-polymer conjugates for dentistry. ACS Appl Polym Mater 2: 1134-1144, 2020. https://doi.org/10.1021/acsapm.9b00921
    Pubmed KoreaMed CrossRef
  44. Kittaka M, Shiba H, Kajiya M, et al: Antimicrobial peptide LL37 promotes vascular endothelial growth factor-a expression in human periodontal ligament cells. J Periodontal Res 48: 228-234, 2013. https://doi.org/10.1111/j.1600-0765.2012.01524.x
    Pubmed CrossRef
  45. Shen X, Al-Baadani MA, He H, et al: Antibacterial and osteogenesis performances of LL37-loaded titania nanopores in vitro and in vivo. Int J Nanomedicine 14: 3043-3054, 2019. https://doi.org/10.2147/ijn.S198583
    Pubmed KoreaMed CrossRef
  46. Zhang L, Fang Z, Li Ql, Cao CY: A tooth-binding antimicrobial peptide to prevent the formation of dental biofilm. J Mater Sci Mater Med 30: 45, 2019. https://doi.org/10.1007/s10856-019-6246-6
    Pubmed CrossRef
  47. Blankenvoorde MF, van't Hof W, Walgreen-Weterings E, et al: Cystatin and cystatin-derived peptides have antibacterial activity against the pathogen Porphyromonas gingivalis. Biol Chem 379: 1371-1375, 1998.
  48. Ganeshnarayan K, Velliyagounder K, Furgang D, Fine DH: Human salivary cystatin SA exhibits antimicrobial effect against Aggregatibacter actinomycetemcomitans. J Periodontal Res 47: 661-673, 2012. https://doi.org/10.1111/j.1600-0765.2012.01481.x
    Pubmed CrossRef
  49. Blancas-Luciano BE, Becker-Fauser I, Zamora-Chimal J, et al: Antimicrobial and anti-inflammatory activity of Cystatin C on human gingival fibroblast incubated with Porphyromonas gingivalis. PeerJ 10: e14232, 2022. https://doi.org/10.7717/peerj.14232
    Pubmed KoreaMed CrossRef
  50. Ahn KB, Kim AR, Kum KY, Yun CH, Han SH: The synthetic human beta-defensin-3 C15 peptide exhibits antimicrobial activity against Streptococcus mutans, both alone and in combination with dental disinfectants. J Microbiol 55: 830-836, 2017. https://doi.org/10.1007/s12275-017-7362-y
    Pubmed CrossRef
  51. Altman H, Steinberg D, Porat Y, et al: In vitro assessment of antimicrobial peptides as potential agents against several oral bacteria. J Antimicrob Chemother 58: 198-201, 2006. https://doi.org/10.1093/jac/dkl181
    Pubmed CrossRef
  52. Allaker RP, Kapas S: Adrenomedullin and mucosal defence: interaction between host and microorganism. Regul Pept 112: 147-152, 2003. https://doi.org/10.1016/S0167-0115(03)00033-8
    Pubmed CrossRef
  53. Soehnlein O, Lindbom L: Neutrophil-derived azurocidin alarms the immune system. J Leukoc Biol 85: 344-351, 2008. https://doi.org/10.1189/jlb.0808495
    Pubmed CrossRef
  54. Fernandes Kenya E, Weeks K, Carter DA: Lactoferrin is broadly active against yeasts and highly synergistic with amphotericin B. Antimicrob Agents Chemother 64: e02284-19, 2020. https://doi.org/10.1128/aac.02284-19
    Pubmed KoreaMed CrossRef
  55. Abrahamson M: Human cysteine proteinase inhibitors: isolation, physiological importance, inhibitory mechanism, gene structure and relation to hereditary cerebral hemorrhage. Scand J Clin Lab Invest 48(sup191): 21-31, 1988. https://doi.org/10.1080/00365518809168291
    CrossRef
  56. Takahashi M, Tezuka T, Katunuma N: Inhibition of growth and cysteine proteinase activity of Staphylococcus aureus V8 by phosphorylated cystatin α in skin cornified envelope. FEBS Lett 355: 275-278, 1994. https://doi.org/10.1016/0014-5793(94)01196-6
    Pubmed CrossRef
  57. Powell WA, Catranis CM, Maynard CA: Synthetic antimicrobial peptide design. Mol Plant Microbe Interact 8: 792-794, 1995. https://doi.org/10.1094/mpmi-8-0792
    Pubmed CrossRef
  58. Ong ZY, Wiradharma N, Yang YY: Strategies employed in the design and optimization of synthetic antimicrobial peptide amphiphiles with enhanced therapeutic potentials. Adv Drug Deliv Rev 78: 28-45, 2014. https://doi.org/10.1016/j.addr.2014.10.013
    Pubmed CrossRef
  59. Lima PG, Oliveira JTA, Amaral JL, Freitas CDT, Souza PFN: Synthetic antimicrobial peptides: characteristics, design, and potential as alternative molecules to overcome microbial resistance. Life Sci 278: 119647, 2021. https://doi.org/10.1016/j.lfs.2021.119647
    Pubmed CrossRef
  60. Chen Y, Guarnieri Michael T, Vasil Adriana I, Vasil Michael L, Mant Colin T, Hodges Robert S: Role of peptide hydrophobicity in the mechanism of action of α-helical antimicrobial peptides. Antimicrob Agents Chemother 51: 1398-1406, 2007. https://doi.org/10.1128/aac.00925-06
    Pubmed KoreaMed CrossRef
  61. Yin LM, Edwards MA, Li J, Yip CM, Deber CM: Roles of hydrophobicity and charge distribution of cationic antimicrobial peptides in peptide-membrane interactions. J Biol Chem 287: 7738-7745, 2012. https://doi.org/10.1074/jbc.M111.303602
    Pubmed KoreaMed CrossRef
  62. Thaker HD, Cankaya A, Scott RW, Tew GN: Role of amphiphilicity in the design of synthetic mimics of antimicrobial peptides with gram-negative activity. ACS Med Chem Lett 4: 481-485, 2013. https://doi.org/10.1021/ml300307b
    Pubmed KoreaMed CrossRef
  63. Sitaram N, Nagaraj R: Interaction of antimicrobial peptides with biological and model membranes: structural and charge requirements for activity. Biochim Biophys Acta 1462: 29-54, 1999. https://doi.org/10.1016/S0005-2736(99)00199-6
    Pubmed CrossRef
  64. Hancock REW: Cationic antimicrobial peptides: towards clinical applications. Expert Opin Investig Drugs 9: 1723-1729, 2000. https://doi.org/10.1517/13543784.9.8.1723
    Pubmed CrossRef
  65. Cutrona KJ, Kaufman BA, Figueroa DM, Elmore DE: Role of arginine and lysine in the antimicrobial mechanism of histone-derived antimicrobial peptides. FEBS Lett 589: 3915-3920, 2015. https://doi.org/10.1016/j.febslet.2015.11.002
    Pubmed KoreaMed CrossRef
  66. Mishra AK, Choi J, Moon E, Baek KH: Tryptophan-rich and proline-rich antimicrobial peptides. Molecules 23: 815, 2018. https://doi.org/10.3390/molecules23040815
    Pubmed KoreaMed CrossRef
  67. Lee TH, Hall KN, Aguilar MI: Antimicrobial peptide structure and mechanism of action: a focus on the role of membrane structure. Curr Top Med Chem 16: 25-39, 2016. https://doi.org/10.2174/1568026615666150703121700
    Pubmed CrossRef
  68. Mai XT, Huang J, Tan J, Huang Y, Chen Y: Effects and mechanisms of the secondary structure on the antimicrobial activity and specificity of antimicrobial peptides. J Pept Sci 21: 561-568, 2015. https://doi.org/10.1002/psc.2767
    Pubmed CrossRef
  69. Chen FY, Lee MT, Huang HW: Sigmoidal concentration dependence of antimicrobial peptide activities: a case study on alamethicin. Biophys J 82: 908-914, 2002. https://doi.org/10.1016/S0006-3495(02)75452-0
    Pubmed KoreaMed CrossRef
  70. Huang HW: Action of antimicrobial peptides:  two-state model. Biochemistry 39: 8347-8352, 2000. https://doi.org/10.1021/bi000946l
    Pubmed CrossRef
  71. Kotnik T, Rems L, Tarek M, Miklavčič D: Membrane electroporation and electropermeabilization: mechanisms and models. Annu Rev Biophys 48: 63-91, 2019. https://doi.org/10.1146/annurev-biophys-052118-115451
    Pubmed CrossRef
  72. Jean-François F, Elezgaray J, Berson P, Vacher P, Dufourc EJ: Pore formation induced by an antimicrobial peptide: electrostatic effects. Biophys J 95: 5748-5756, 2008. https://doi.org/10.1529/biophysj.108.136655
    Pubmed KoreaMed CrossRef
  73. Tossi A, Sandri L, Giangaspero A: Amphipathic, α-helical antimicrobial peptides. Biopolymers 55: 4-30, 2000. https://doi.org/10.1002/1097-0282(2000)55:1<4::AID-BIP30>3.0.CO;2-M
    Pubmed CrossRef
  74. Piers KL, Hancock REW: The interaction of a recombinant cecropin/melittin hybrid peptide with the outer membrane of Pseudomonas aeruginosa. Mol Microbiol 12: 951-958, 1994. https://doi.org/10.1111/j.1365-2958.1994.tb01083.x
    Pubmed CrossRef
  75. Oren Z, Shai Y: Mode of action of linear amphipathic α-helical antimicrobial peptides. Biopolymers 47: 451-463, 1998. https://doi.org/10.1002/(SICI)1097-0282(1998)47:6<451::AID-BIP4>3.0.CO;2-F
    CrossRef
  76. Shai Y: Mechanism of the binding, insertion and destabilization of phospholipid bilayer membranes by α-helical antimicrobial and cell non-selective membrane-lytic peptides. Biochim Biophys Acta 1462: 55-70, 1999. https://doi.org/10.1016/S0005-2736(99)00200-X
    CrossRef
  77. Le CF, Fang CM, Sekaran Shamala D: Intracellular targeting mechanisms by antimicrobial peptides. Antimicrob Agents Chemother 61: e02340-16, 2017. https://doi.org/10.1128/aac.02340-16
    Pubmed KoreaMed CrossRef
  78. Nicolas P: Multifunctional host defense peptides: intracellular-targeting antimicrobial peptides. FEBS J 276: 6483-6496, 2009. https://doi.org/10.1111/j.1742-4658.2009.07359.x
    Pubmed CrossRef
  79. Aoki W, Ueda M: Characterization of antimicrobial peptides toward the development of novel antibiotics. Pharmaceuticals 6: 1055-1081, 2013. https://doi.org/10.3390/ph6081055
    Pubmed KoreaMed CrossRef
  80. Hong SY, Oh JE, Kwon M, et al: Identification and characterization of novel antimicrobial decapeptides generated by combinatorial chemistry. Antimicrob Agents Chemother 42: 2534-2541, 1998. https://doi.org/10.1128/aac.42.10.2534
    Pubmed KoreaMed CrossRef
  81. Marcos JF, Muñoz A, Pérez-Payá E, Misra S, López-García B: Identification and rational design of novel antimicrobial peptides for plant protection. Annu Rev Phytopathol 46: 273-301, 2008. https://doi.org/10.1146/annurev.phyto.121307.094843
    Pubmed CrossRef
  82. Zhang C, Yang M: Antimicrobial peptides: from design to clinical application. Antibiotics 11: 349, 2022. https://doi.org/10.3390/antibiotics11030349
    Pubmed KoreaMed CrossRef
  83. Merrifield RB, Vizioli LD, Boman HG: Synthesis of the antibacterial peptide cecropin A(1-33). Biochemistry 21: 5020-5031, 1982. https://doi.org/10.1021/bi00263a028
    Pubmed CrossRef
  84. Eckert R: Road to clinical efficacy: challenges and novel strategies for antimicrobial peptide development. Future Microbiol 6: 635-651, 2011. https://doi.org/10.2217/fmb.11.27
    Pubmed CrossRef
  85. Shao C, Zhu Y, Lai Z, Tan P, Shan A: Antimicrobial peptides with protease stability: progress and perspective. Future Med Chem 11: 2047-2050, 2019. https://doi.org/10.4155/fmc-2019-0167
    Pubmed CrossRef
  86. Gan BH, Gaynord J, Rowe SM, Deingruber T, Spring DR: The multifaceted nature of antimicrobial peptides: current synthetic chemistry approaches and future directions. Chem Soc Rev 50: 7820-7880, 2021. https://doi.org/10.1039/D0CS00729C
    Pubmed KoreaMed CrossRef
  87. Franzman MR, Burnell KK, Dehkordi-Vakil FH, Guthmiller JM, Dawson DV, Brogden KA: Targeted antimicrobial activity of a specific IgG-SMAP28 conjugate against Porphyromonas gingivalis in a mixed culture. Int J Antimicrob Agents 33: 14-20, 2009. https://doi.org/10.1016/j.ijantimicag.2008.05.021
    Pubmed KoreaMed CrossRef
  88. Liu Y, Wang L, Zhou X, Hu S, Zhang S, Wu H: Effect of the antimicrobial decapeptide KSL on the growth of oral pathogens and Streptococcus mutans biofilm. Int J Antimicrob Agents 37: 33-38, 2011. https://doi.org/10.1016/j.ijantimicag.2010.08.014
    Pubmed CrossRef
  89. Li H, Cheng JW, Yu HY, Xin Y, Tang L, Ma Y: Effect of the antimicrobial peptide D-Nal-Pac-525 on the growth of Streptococcus mutans and its biofilm formation. J Microbiol Biotechnol 23: 1070-1075, 2013. https://doi.org/10.4014/jmb.1212.12035
    Pubmed CrossRef
  90. Wang HY, Cheng JW, Yu HY, Lin L, Chih YH, Pan YP: Efficacy of a novel antimicrobial peptide against periodontal pathogens in both planktonic and polymicrobial biofilm states. Acta Biomaterialia 25: 150-161, 2015. https://doi.org/10.1016/j.actbio.2015.07.031
    Pubmed CrossRef
  91. Suwandecha T, Srichana T, Balekar N, Nakpheng T, Pangsomboon K: Novel antimicrobial peptide specifically active against Porphyromonas gingivalis. Arch Microbiol 197: 899-909, 2015. https://doi.org/10.1007/s00203-015-1126-z
    Pubmed CrossRef
  92. Tu H, Fan Y, Lv X, Han S, Zhou X, Zhang L: Activity of synthetic antimicrobial peptide GH12 against oral streptococci. Caries Res 50: 48-61, 2016. https://doi.org/10.1159/000442898
    Pubmed CrossRef
  93. Chen L, Jia L, Zhang Q, et al: A novel antimicrobial peptide against dental-caries-associated bacteria. Anaerobe 47: 165-172, 2017. https://doi.org/10.1016/j.anaerobe.2017.05.016
    Pubmed CrossRef
  94. Maldonado A, Ruiz-Barba José L, Jiménez-Díaz R: Purification and genetic characterization of plantaricin NC8, a novel coculture-inducible two-peptide bacteriocin from Lactobacillus plantarum NC8. Appl Environ Microbiol 69: 383-389, 2003. https://doi.org/10.1128/AEM.69.1.383-389.2003
    Pubmed KoreaMed CrossRef
  95. Khalaf H, Nakka SS, Sandén C, et al: Antibacterial effects of Lactobacillus and bacteriocin PLNC8 αβ on the periodontal pathogen Porphyromonas gingivalis. BMC Microbiol 16: 188, 2016. https://doi.org/10.1186/s12866-016-0810-8
    Pubmed KoreaMed CrossRef
  96. Taniguchi M, Ochiai A, Takahashi K, et al: Antimicrobial activity against Porphyromonas gingivalis and mechanism of action of the cationic octadecapeptide AmyI-1-18 and its amino acid-substituted analogs. J Biosci Bioeng 122: 652-659, 2016. https://doi.org/10.1016/j.jbiosc.2016.05.008
    Pubmed CrossRef
  97. Matsugishi A, Aoki-Nonaka Y, Yokoji-Takeuchi M, et al: Rice peptide with amino acid substitution inhibits biofilm formation by Porphyromonas gingivalis and Fusobacterium nucleatum. Arch Oral Biol 121: 104956, 2021. https://doi.org/10.1016/j.archoralbio.2020.104956
    Pubmed CrossRef
  98. Liang D, Li H, Xu X, Liang J, Dai X, Zhao W: Rational design of peptides with enhanced antimicrobial and anti-biofilm activities against cariogenic bacterium Streptococcus mutans. Chem Biol Drug Des 94: 1768-1781, 2019. https://doi.org/10.1111/cbdd.13579
    Pubmed CrossRef
  99. Feng Z, Luo J, Lyu X, Chen Y, Zhang L: Selective antibacterial activity of a novel lactotransferrin-derived antimicrobial peptide LF-1 against Streptococcus mutans. Arch Oral Biol 139: 105446, 2022. https://doi.org/10.1016/j.archoralbio.2022.105446
    Pubmed CrossRef
  100. Jiang SJ, Xiao X, Zheng J, et al: Antibacterial and antibiofilm activities of novel antimicrobial peptide DP7 against the periodontal pathogen Porphyromonas gingivalis. J Appl Microbiol 133: 1052-1062, 2022. https://doi.org/10.1111/jam.15614
    Pubmed CrossRef
  101. Sullivan R, Santarpia P, Lavender S, et al: Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: targeted elimination of Streptococcus mutans and prevention of demineralization. Caries Res 45: 415-428, 2011. https://doi.org/10.1159/000330510
    Pubmed KoreaMed CrossRef
  102. Jiang S, Zha Y, Zhao T, et al: Antimicrobial peptide temporin derivatives inhibit biofilm formation and virulence factor expression of Streptococcus mutans. Front Microbiol 14: 1267389, 2023. https://doi.org/10.3389/fmicb.2023.1267389
    Pubmed KoreaMed CrossRef
  103. Qi S, Zhao S, Zhang H, et al: Novel casein antimicrobial peptides for the inhibition of oral pathogenic bacteria. Food Chem 425: 136454, 2023. https://doi.org/10.1016/j.foodchem.2023.136454
    Pubmed CrossRef
  104. Kazemzadeh-Narbat M, Kindrachuk J, Duan K, Jenssen H, Hancock REW, Wang R: Antimicrobial peptides on calcium phosphate-coated titanium for the prevention of implant-associated infections. Biomaterials 31: 9519-9526, 2010. https://doi.org/10.1016/j.biomaterials.2010.08.035
    Pubmed CrossRef
  105. Kazemzadeh-Narbat M, Noordin S, Masri BA, et al: Drug release and bone growth studies of antimicrobial peptide-loaded calcium phosphate coating on titanium. J Biomed Mater Res B Appl Biomater 100B: 1344-1352, 2012. https://doi.org/10.1002/jbm.b.32701
    Pubmed CrossRef
  106. Genco CA, Maloy WL, Kari UP, Motley M: Antimicrobial activity of magainin analogues against anaerobic oral pathogens. Int J Antimicrob Agents 21: 75-78, 2003. https://doi.org/10.1016/S0924-8579(02)00275-3
    Pubmed CrossRef
  107. Semreen MH, El-Gamal MI, Abdin S, et al: Recent updates of marine antimicrobial peptides. Saudi Pharm J 26: 396-409, 2018. https://doi.org/10.1016/j.jsps.2018.01.001
    Pubmed KoreaMed CrossRef
  108. Moreno M, Giralt E: Three valuable peptides from bee and wasp venoms for therapeutic and biotechnological use: melittin, apamin and mastoparan. Toxins 7: 1126-1150, 2015. https://doi.org/10.3390/toxins7041126
    Pubmed KoreaMed CrossRef
  109. Han SM, Kim JM, Hong IP, et al: Antibacterial activity and antibiotic-enhancing effects of honeybee venom against methicillin-resistant Staphylococcus aureus. Molecules 21: 79, 2016. https://doi.org/10.3390/molecules21010079
    Pubmed KoreaMed CrossRef
  110. Lee G, Bae H: Anti-inflammatory applications of melittin, a major component of bee venom: detailed mechanism of action and adverse effects. Molecules 21: 616, 2016. https://doi.org/10.3390/molecules21050616
    Pubmed KoreaMed CrossRef
  111. Memariani H, Memariani M, Pourmand MR: Venom-derived peptide Mastoparan-1 eradicates planktonic and biofilm-embedded methicillin-resistant Staphylococcus aureus isolates. Microb Pathog 119: 72-80, 2018. https://doi.org/10.1016/j.micpath.2018.04.008
    Pubmed CrossRef
  112. Piktel E, Wnorowska U, Gorbacz-Konończuk J, et al: From antimicrobial to anticancer: unraveling the potential of pleurocidin and pleurocidin-derived peptides in the treatment of cancers. Front Pharmacol 15: 1340029, 2024. https://doi.org/10.3389/fphar.2024.1340029
    Pubmed KoreaMed CrossRef
  113. El Karim IA, Linden GJ, Orr DF, Lundy FT: Antimicrobial activity of neuropeptides against a range of micro-organisms from skin, oral, respiratory and gastrointestinal tract sites. J Neuroimmunol 200: 11-16, 2008. https://doi.org/10.1016/j.jneuroim.2008.05.014
    Pubmed CrossRef
  114. Li JY, Wang XJ, Wang LN, et al: High in vitro antibacterial activity of Pac-525 against Porphyromonas gingivalis biofilms cultured on titanium. Biomed Res Int 2015: 909870, 2015. https://doi.org/10.1155/2015/909870
    Pubmed KoreaMed CrossRef
  115. Zhu Y, Hao W, Wang X, et al: Antimicrobial peptides, conventional antibiotics, and their synergistic utility for the treatment of drug-resistant infections. Med Res Rev 42: 1377-1422, 2022. https://doi.org/10.1002/med.21879
    Pubmed CrossRef
  116. Lobos O, Padilla A, Padilla C: In vitro antimicrobial effect of bacteriocin PsVP-10 in combination with chlorhexidine and triclosan against Streptococcus mutans and Streptococcus sobrinus strains. Arch Oral Biol 54: 230-234, 2009. https://doi.org/10.1016/j.archoralbio.2008.11.007
    Pubmed CrossRef
  117. Andersson DI: Persistence of antibiotic resistant bacteria. Curr Opin Microbiol 6: 452-456, 2003. https://doi.org/10.1016/j.mib.2003.09.001
    Pubmed CrossRef
  118. Hassan M, Kjos M, Nes IF, Diep DB, Lotfipour F: Natural antimicrobial peptides from bacteria: characteristics and potential applications to fight against antibiotic resistance. J Appl Microbiol 113: 723-736, 2012. https://doi.org/10.1111/j.1365-2672.2012.05338.x
    Pubmed CrossRef
  119. Drexelius MG, Neundorf I: Application of antimicrobial peptides on biomedical implants: three ways to pursue peptide coatings. Int J Mol Sci 22: 13212, 2021. https://doi.org/10.3390/ijms222413212
    Pubmed KoreaMed CrossRef
  120. Noore J, Noore A, Li B: Cationic antimicrobial peptide LL-37 is effective against both extra- and intracellular Staphylococcus aureus. Antimicrob Agents Chemother 57: 1283-1290, 2013. https://doi.org/10.1128/aac.01650-12
    Pubmed KoreaMed CrossRef
  121. Pasupuleti M, Schmidtchen A, Malmsten M: Antimicrobial peptides: key components of the innate immune system. Crit Rev Biotechnol 32: 143-171, 2012. https://doi.org/10.3109/07388551.2011.594423
    Pubmed CrossRef
  122. Ganz T: The role of antimicrobial peptides in innate immunity. Integr Comp Biol 43: 300-304, 2003. https://doi.org/10.1093/icb/43.2.300
    Pubmed CrossRef
  123. Cederlund A, Gudmundsson GH, Agerberth B: Antimicrobial peptides important in innate immunity. FEBS J 278: 3942-3951, 2011. https://doi.org/10.1111/j.1742-4658.2011.08302.x
    Pubmed CrossRef
  124. Lindhe J, Meyle J; Group D of European Workshop on Periodontology: Peri-implant diseases: consensus report of the Sixth European Workshop on Periodontology. J Clin Periodontol 35(8 Suppl): 282-285, 2008. https://doi.org/10.1111/j.1600-051X.2008.01283.x
    Pubmed CrossRef
  125. Schwarz F, Derks J, Monje A, Wang HL: Peri-implantitis. J Clin Periodontol 45: S246-S266, 2018. https://doi.org/10.1111/jcpe.12954
    CrossRef
  126. Heitz-Mayfield LJ, Mombelli A: The therapy of peri-implantitis: a systematic review. Int J Oral Maxillofac Implants 29 Suppl: 325-345, 2014. https://doi.org/10.11607/jomi.2014suppl.g5.3
    Pubmed CrossRef
  127. Fang D, Yuran S, Reches M, Catunda R, Levin L, Febbraio M: A peptide coating preventing the attachment of Porphyromonas gingivalis on the surfaces of dental implants. J Periodontal Res 55: 503-510, 2020. https://doi.org/10.1111/jre.12737
    Pubmed CrossRef
  128. Dong H, Liu H, Zhou N, et al: Surface modified techniques and emerging functional coating of dental implants. Coatings 10: 1012, 2020. https://doi.org/10.3390/coatings10111012
    CrossRef
  129. Körtvélyessy G, Tarjányi T, Baráth ZL, Minarovits J, Tóth Z: Bioactive coatings for dental implants: a review of alternative strategies to prevent peri-implantitis induced by anaerobic bacteria. Anaerobe 70: 102404, 2021. https://doi.org/10.1016/j.anaerobe.2021.102404
    Pubmed CrossRef
  130. Geng H, Yuan Y, Adayi A, et al: Engineered chimeric peptides with antimicrobial and titanium-binding functions to inhibit biofilm formation on Ti implants. Mater Sci Eng C Mater Biol Appl 82: 141-154, 2018. https://doi.org/10.1016/j.msec.2017.08.062
    Pubmed CrossRef


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